Intralumenal drug eluting prosthesis

ABSTRACT

A prosthesis for insertion into a lumen to limit restenosis of the lumen. The prosthesis carries restenosis-limiting drugs which elute after the device is positioned in the lumen.

This is a divisional of application(s) Ser. No. 08/429,966 filed on Apr.27, 1995, pending, which is a divisional of Ser. No. 08/171,361 filed onDec. 21, 1993 now U.S. Pat. No. 5,545,208, which is acontinuation-in-part of Ser. No. 07/815,560 filed on Dec. 27, 1991,abandoned, which is a continuation of Ser. No. 07/486,580, filed on Feb.28, 1990, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention related to methods for lessening restenosis of bodylumens, and to prosthesis for delivering drugs to treat said restenosis.

2. Description of the Related Art

Restenosis is defined as the reclosure of a previously stenosed anssubsequently dilated peripheral or coronary vessel. It occurs at a rateof 20-50% for these procedures and is dependent on a number of clinicaland morphological variables. Restenosis may begin shortly following anangioplasty procedure, but usually ceases at the end of approximatelysix (6) months. There is not a current therapeutic procedure that hasbeen proven to significantly reduce this restenosis rate.

A recent technology that has been developed that assesses the problem ofrestenosis is intravascular stents. Stents are typically metallicdevices that are permanently implanted (expanded) in coronary andperipheral vessels. The goal of these stents is to provide a long-term"scaffolding" or support for the diseased (stenosed) vessels. The theorybeing, if you can support the vessel from the inside, the vessel willnot close down or restenose. Unfortunately, initial data from clinicalstent implants indicates that these metallic structures are not verysuccessful in reducing restenosis.

Pharmacologic (biochemical) attempts have been made to reduce the rateof restenosis. All of these attempts have dealt with the systemicdelivery of drugs via oral, intravascular or intramuscular introduction.Little, if any success has been achieved with this systemic approach.

For drug delivery, it has been recognized for a long period of time thatpills and injections may not be the best mode of administration. It isvery difficult with these types of administration to obtain constantdrug delivery. Patient noncompliance with instructions is also aproblem. Through repeated does, these drugs often cycle throughconcentration peaks and valleys, resulting in time periods of toxicityand ineffectiveness. Thus, localized drug treatment is warranted.

SUMMARY OF THE INVENTION

The invention provides prostheses which may be inserted into a lumen ofa body and fixed to the lumen wall adjacent an area needing treatment.Most typically, the lumen will be part of the vascular system which maybe subject to restenosis following angioplasty. However, the methods anddevices of the invention are also suited to treatment of any body lumen,including the vas deferens, ducts of the gallbladder, prostate gland,trachea, bronchus and liver or any other lumen of the body wheremedication cannot be applied without a surgical procedure. The inventionapplies to acute and chronic closure or reclosure of body lumens.

The prostheses of the invention include at least one drug which willrelease from the device at a controlled rate to supply the drug whereneeded without the overkill of systemic delivery. The prostheses includemeans for fixing the device in the lumen where desired. The prosthesesmay be completely biodegradable or may be bioabsorbable in whole orincorporated into the lumen wall as a result of tissue over growth,i.e., endothelialization. Alternatively, the prostheses may be biostablein which case the drug is diffused out from the biostable materials inwhich it is incorporated.

The prosthesis comprises a generally flexible tubular body which isfixed against the lumen wails by a mechanical action. The device shouldnot cause an appreciable reduction in the lumen cross-section whereinserted. Conventional stent designs which provide an expansion of thevessel are suitable, though not required. In all cases, the prosthesesof the invention require the presence of an elutable drug compounded tothe prosthesis itself. With conventional metal stents, the inventionrequires a drug-carrying coating overlying at least a portion of themetal.

The drugs in the prosthesis may be of any type which would be useful intreating the lumen. In order to prevent restenosis in blood vessels,migration and subsequent proliferation of smooth muscle cells must bechecked. Platelet aggregation and adhesion can be controlled withantiplatelets and anticoagulants. Growth factor and receptor blockersand antagonists may be used to limit the normal repair response.

The current invention contemplates the usage of any prosthesis whichelutes drugs locally to treat a lumen in need of repair. Controlledrelease, via a bioabsorbable polymer, offers to maintain the drug levelwithin the desired therapeutic range for the duration of the treatment.When "stent" is referred to herein, it may include the classicaldefinition of stents as they are used in intravascular applications."Stent" used herein also includes any prothesis which may be insertedand held where desired in a lumen. It includes, but is not limited to,structures such as those shown and described in U.S. Pat. No. 4,886,062to Wiktor.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of the invention is hereafter described withspecific reference being made to the drawings in which:

FIG. 1 is a greatly enlarged side view of an intralumenal drug-elutingprosthesis of the invention;

FIG. 2 is a greatly enlarged side view of an alternative embodiment tothe prosthesis of FIG. 1;

FIG. 3A is a greatly enlarged fragment of the embodiment of FIG. 1;

FIG. 3B is a greatly enlarged fragment of the embodiment of FIG. 1 inwhich two layers of polymers are present, each having a different drug;

FIG. 4 is a greatly enlarged fragment of the embodiment of FIG. 2;

FIG. 5 is a greatly enlarged microscopic fragmentary detail of drugshown eluting form the porous structure of a filament or filamentcoating in a prosthesis into tissue or the vessel lumen;

FIG. 6 is a greatly enlarged cross-section of a blood vessel showingplaque profile immediately post-balloon catheter dilation procedure;

FIG. 7 is a greatly enlarged cross-section of the subject of FIG. 6 at alater date showing restenosis;

FIG. 8 is a greatly enlarged cross-section of a blood vessel showingplaque-prosthesis profile immediately post-prosthesis implant procedure;

FIG. 9 is a greatly enlarged cross-section of the subject of FIG. 8after ingrowth has occurred;

FIG. 10 is a greatly enlarged fragmentary perspective view of a bloodvessel wall and prosthesis filament of FIGS. 1 and 3 immediately afterimplantation;

FIG. 11 is a greatly enlarged fragmentary perspective view of thesubject of FIG. 10 after about one month;

FIG. 12 is a greatly enlarged fragment of a loose weave of prosthesisfilaments;

FIG. 13 is a greatly enlarged fragment of a coated metal filament in aloose weave;

FIG. 14 is a greatly enlarged fragment of a melted junction weave ofprosthesis filaments in a loose weave;

FIG. 15 is a greatly enlarged fragment of a kinked junction wave ofprosthesis filaments;

FIG. 16 is a greatly enlarged fragment of multistrand weave ofprosthesis filaments; and

FIG. 17 is a alternative embodiment to FIG. 16, in which strands are notwoven.

FIG. 18 is a partial sectional view of a catheter for delivery of theprosthesis of the present invention.

FIG. 19a-19i are sectional views of the deployment of the prosthesis bythe catheter of FIG. 18.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Restenosis

In the discussion above, a very simple definition of restenosis wasgiven. As a complement to this definition, there are several moreclinical definitions. Several of these definitions are listed below:

1. Reduction of minimal luminal diameter to less than 50% of the normallumen diameter.

2. Loss of at least 50% of the initial gain achieved in angioplasty.

3. Decrease of at least 30% in the lumen diameter compared topost-angioplasty result.

4. A return to within 10% of the pre-angioplasty diameter stenosis.

5. An immediate post angioplasty diameter stenosis of less than 50% thatincreases to 70% or greater at follow-up.

6. Deterioration of 0.72 mm in minimal luminal diameter or greater frompost-angioplasty to follow-up.

7. As for 6, but with a deterioration of 0.5 mm.

These definitions are sued by cardiologists to angiographically definerestenosis.

Several hypotheses exist on why and how restenosis occurs. The current,most widely accepted explanation is that restenosis is a natural healingprocess in response to the arterial injury that occurs during all typesof angioplasty procedures. This very complex healing process results inintimal hyperplasia, more specifically migration and proliferation ofmedial smooth muscle cells (SMC). The problem associated with thisarterial healing process is that in some instances, it does not shutoff. The artery continues to "heal" until it becomes occluded. It shouldbe noted that restenosis is not a re-deposition of the plaque-likecholesterol material that originally occluded the artery.

The following is a possible scenario for restenosis according to thevessel healing hypothesis. Successful angioplasty of stenotic lesionsproduces cracking of the plaque, dissection into the media, denudationand destruction of endothelial cells, exposure of thrombogenic collagen,released tissue thromboplastin, and an increased loss of prostacyclinproduction. All of these lead to the aggregation of active platelets.

FIGS. 6 and 7 show a typical vessel 30 in cross-section afterangioplasty procedures showing the interior 32 of the lumen. In FIG. 6the interior of the lumen is rough and includes intimal flaps 34. Damagecauses healing with deposition of platelets, fibrin formation andproliferation of neointima 37 which as shown in FIG. 7 significantlyreduces the interior of the lumen.

Activated platelets release several mitogens including platelet derivedgrowth factor (PDGF), epidermal growth factor, and transforming growthfactor. PDGF has both mitogenic and chemotactic properties and thus, mayinduce both mitigation of SMC from the medial layer to the intimal layeras well as proliferation (Intimal hyperplasia). PDGF causes SMCproliferation by binding to specific PDGF receptors. Once the PDGF isbound to the receptors, deoxyribose nucleic acid (DNA) synthesis occursand new cells are replicated. Minor endothelial injury may causeplatelet adhesion and activation with the resultant release of PDGF.Thus, even the deposition of a monolayer of platelets may be sufficientto induce SMC proliferation.

Deeper arterial injury which is sometimes associated with complexstenotic lesions leads to more extensive platelet deposition andactivation which may cause an even greater availability of the mitogenicfactors. Thus, increased SMC proliferation and intimal hyperplasia.Arterial injury from angioplasty may result in release of PDGF-likecompounds from not only platelets but also macrophages, monocytes,endothelial cells, or SMC's themselves.

Activated SMC from human atheroma or following experimental arterialinjury secrete PDGF-like molecules which appears to lead to selfperpetuation of SMC proliferation by the release of their own PDGF-likesubstances. Thus, any or all of the cells which can secrete PDGF relatesubstances (platelets, macrophages, monocytes, endothelia, and smoothmuscle cells) may contribute to the cascading effect of restenosis afterangioplasty.

The previous restenosis scenario resulted from normal angioplastyprocedures. During balloon angioplasty if the balloon is undersized ornot totally inflated and the plaque cracking and extensive endothelialdenudation does not occur the lesion could still restenose. Rheologicfactors contribute as well to the interaction between platelets and thearterial wall. Residual stenosis, resulting from inadequate balloonexpansion, produces a high local shear rate and enhances plateletdeposition and activation. These stenoses may be important as a stimulusfor some proliferation through enhanced platelet deposition andsecretion of growth factors. This hypothesis correlates with theincreased incidence of restenosis in patients with high-grade residualstenoses or transtenotic gradients.

Prevention of Restenosis

In order to prevent restenosis, one must stop the proliferation ofsmooth muscle cells. As stated earlier, this is a biochemical processwhich cannot be treated mechanically. Several hypothesis exist on how tobiochemically stop restenosis. Some of which are:

1. Reduce the adhesion and aggregation of the platelets at the arterialinjury site.

2. Block the expression of the growth factors and their receptors.

3. Develop competitive antagonists of the above growth factors.

4. Interfere with the receptor signaling in the responsive cell.

5. Find a "natural" inhibitor of smooth muscle proliferation.

Item #1 is directly related to the formation of thrombus, a majorproblem with all types of angioplasty procedures. Items #2, #3 and #4are closely related. They deal with blocking restenosis during themassive cell migration and replication cycle. Unlike item #1, theseitems address the growth factors that are produced from sources otherthan platelets. Item #5 is listed to address the question; Why don't50-80% of the people undergoing angioplasty restenose? There may be sometype of natural inhibitor that these people produce that stops theproliferation of smooth muscle cells.

There are at least two (2) different ways to prevent the adhesion andaggregation of platelets. One method is to use an antiplatelet andanother is to use an anticoagulant.

Antiplatelet drugs include such as aspirin and dipyridamole. Aspirin isclassified as an analgesic, antipyretic, anti-inflammatory, antiplateletdrug. It has been clinically tested and proven to reduce the risk ofsudden death and/or non-fatal reinfarction in post myocardial infarction(heart attack) patients. The proposed mechanism of how aspirin works,relates directly to the platelets. It somehow blocks the platelets,restricting coagulation. This prevents the cascading plateletaggregation found in thrombus and subsequently restenosis. Aspirin istherefore a possible restenosis inhibitor. Dipyridamole is a drugsimilar to aspirin, in that is has anti-platelet characteristics.Dipyridamole is also classified as a coronary vasodilator. It increasescoronary blood flow by primary selective dilatation of the coronaryarteries without altering systemic blood pressure or blood flow inperipheral arteries. These vasodilation characteristics are thought tobe possibly beneficial for restenosis prevention.

Anticoagulant drugs include Heparin, Coumadin, Protamine, and Hirudin.Heparin is the most common anticoagulant used today. Heparin, in oneform or another, is used in virtually every angioplasty procedureperformed. All four (4) of these drugs function as an anticoagulant bypreventing the production of thrombin, a binding agent which causesblood to clot. This too, may reduce the cascading effect of plateletaggregation at the lesion site, thus possibly reducing restenosis. Theuse of Protamine in the presence of Heparin causes the Protamine tofunction as a Heparin antagonist, blocking the effect of the Heparin.Protamine, however, used alone, acts as an anticoagulant. Hirudin issingled out because it is not normally found in the human body. Hirudinis a drug that is found in the salivary glands of leeches. It is a veryconcentrated anticoagulant that functions in a similar manner asHeparin, Coumadin, and Protamine.

There are several types of drugs that interrupt cell replication.Antimitotics (cytotoxic agents) work directly to prevent cell mitosis(replication), whereas antimetabolites prevent deoxyribose nucleic acid(DNA) synthesis, thus preventing replication. The action of theantimitotics and antimetabolites are similar, they can be grouped intoone category. This category will be known as the anti-replicate drugs.

Anti-replicate drugs include among others: Methotrexate, Colchicine,Azathioprine, Vincristine, VinBlastine, Fluorouracil, Adriamycin, andMutamycin. The target systemic molarity desired with methotrexate is onthe order of 10⁻⁶ M with a range of between 10⁻³ to 10⁻⁸ Molar. Locally,the molarity of the drug may be highly variable, which is one of thegreat disadvantages in systemic administration of the drug. When drugsare delivered locally via the prosthesis of the invention, they may beat therapeutic levels at the diseased site while at the lower limits ofdetectability in the bloodstream. So little drug is required foreffective local treatment of a lumen that the drug may not be detectablein blood samples.

Anti-inflammatory drugs such as glucocorticoids (e.g., dexamethasone,betamethasone) can also be useful to locally suppress inflammationcaused by injury to luminal tissue during angioplasty.

If the restenosis process ranges from shortly after injury to about fourto six months later, then the generalized elution rates contemplated aresuch that the drug should ideally start to be released immediately afterthe prosthesis is secured to the lumen wall to lessen cellproliferation. The drug should then continue to elute for up to aboutfour to six months in total.

Complex systems of drugs may be carried by the prosthesis. Ananticoagulant or antiplatelet may be included in the outermost surfaceof the device in order to elute off very quickly for the first severaldays. Antiinflammatories and antireplicates can be formulated into thedevice to continue to elute later, when in contact with non-blood cellsafter neointima overgrowth has surrounded the device. This usuallyoccurs in about two weeks. The drug elution rate does not need to beuniform, and may be tailored to fit the need of the patient.

Prosthesis (Stent) Design

The current invention contemplates the usage of any prosthesis whichelutes drugs locally to treat a lumen in need of repair. When "stent" isreferred to herein, it may include the classical definition of stents asthey are used in intravascular applications. "Stent" used herein alsoincludes any prosthesis which may be inserted and held where desired ina lumen.

FIGS. 1 through 17 show features of some of the prostheses which may beused to carry and elute restenosis limiting-drugs.

The current preferred stent 10 configuration consists of a single filar,monofilament braided mesh design as shown in FIG. 1. There are sixteen(16) filaments 12, eight (8) of which are wound in one helicaldirection, and the remaining eight (8) which are wound in the oppositedirection. The stent 10 is self-expanding to a predetermined diameter.The profile (diameter) of the stent 10 can be easily reduced by pullingthe stent 10 longitudinally. In this reduced profile configuration, thestent 10 can be loaded into a catheter for delivery into the vessel.

The stent 20 shown in FIGS. 2 and 4 is a metallic malleable design whichmay be forced against a lumen wall by a balloon catheter which fixes itinto position. The exterior surface of the metal filaments 22 wouldinclude a coating 14 with a drug-eluting polymer described previously.The polymer may be biostable or bioabsorbable. If biostable, the drugwould diffuse out of the polymer.

The variations of design shown in the embodiments of FIGS. 1 and 2 showthat the prosthesis of the invention must be secured against a lumenwall and must carry a drug-eluting polymer.

There are many variables in the design of stent 10. The angle (α) of thefilaments 12 is a major variable. The angle α can vary from 0 degrees to180 degrees. The design in the Figures is based on an angle in the 60degree to 90 degree range.

There are many options for fabricating the drug eluting stents. Oneoption is to have all sixteen (16) filaments be drug eluting. Or, youcould have any number of filaments up to sixteen (16) degrade and elutedrugs. Another option is to have a multi-filar stent. Instead of asingle filament braided into the stent, it is possible to have two (2),three (3), or even four (4) strands 16 braided to form a filament 12 asshown in FIG. 16. This would create a stent with much greater expansileforce, but also have much more material in the surface area. This is acommon trade-off in stent design. Similar to the single-filar design,the multi-filar form shown in FIG. 16 could have varying numbers ofstrands 16 that are drug eluting. FIGS. 16 and 17 show that themulti-filar design may be braided or unbraided. One (1), two (2), three(3), or four (4) of the filaments could be impregnated with a drug andbiodegradably elute. Alternatively, the polymer may be biostable whichallows for diffusion of the drug without degradation.

The stent 10 of FIG. 1 consists of a wound braided mesh which isself-expanding to a predetermined diameter and whose profile diametercan be greatly reduced for catheter introduction. The radial expansileforce increases with diameter to the point of the self-expanded diameterlimit, at which point the angle between the filaments and thelongitudinal axis is a maximum. FIGS. 12 and 15 show alternativeconstruction techniques to alter the radial expansive force. FIG. 12shows the filaments 12 being woven without any connection. FIG. 13 issimilar except the filament 22 is formed with a metal core 16 and acoating 14. In FIG. 14 the individual filaments 12 are shown with abonded juncture 18. The bonding at the juncture 18 prevents theindividual filaments 12 from sliding relative to each other, whichimproves the radial strength. The mechanically kinked junction 19 shownin FIG. 15 also limits the sliding of the filaments to change the radialstrength. A heated platen press may be pressed against the wound stentwhile still on the forming mandrel to form the kinks. Highertemperatures may be used to form the melted junctures 18.

The devices may be made more visible under fluoroscopy and x-ray byincorporating radiopaque materials into marker band 24 to the individualfilaments 12 at the ends of the stent 10 as shown in FIG. 1. Such markerbands could help to locate the stent and assure proper placement andpatency.

Bioabsorbable Prosthesis (Stent) Materials

Controlled release, via a bioabsorbable polymer, offers to maintain thedrug level within the desired therapeutic range for the duration of thetreatment. In the case of stents, the prosthesis materials will maintainvessel support for at least two weeks or until incorporated into thevessel wall even with bioabsorbable, biodegradable polymerconstructions.

Several polymeric compounds that are known to be bioabsorbable andhypothetically have the ability to be drug impregnated may be useful inprosthesis formation herein. These compounds include: poly-1-lacticacid/polyglycolic acid, polyanhydride, and polyphosphate ester. A briefdescription of each is given below.

Poly-1-lactic acid/polyglycolic acid has been used for many years in thearea of bioabsorbable sutures. It is currently available in many forms,i.e., crystals, fibers, blocks, plates, etc. These compounds degradeinto non-toxic lactic and glycolic acids. There are, however, severalproblems with this compound. The degradation artifacts (lactic acid andglycolic acid) are slightly acidic. The acidity causes minorinflammation in the tissues as the polymer degrades. This sameinflammation could be very detrimental in coronary and peripheralarteries, i.e., vessel occlusion. Another problem associated with thispolymer is the ability to control and predict the degradation behavior.It is not possible for the biochemist to safely predict degradationtime. This could be very detrimental for a drug delivery device.

Another compound which could be used are the polyanhydrides. They arecurrently being used with several chemotherapy drugs for the treatmentof cancerous tumors. These drugs are compounded into the polymer whichis molded into a cube-like structure and surgically implanted at thetumor site.

Polyanhydrides have weaknesses in their mechanical properties, due tolow molecular weights. This drawback makes them difficult to processinto a filament form. Also, polyanhydrides have poor solubility, makingcharacterization and fabrication difficult.

The compound which is preferred is a polyphosphate ester. Polyphosphateester is a compound such as that disclosed in U.S. Pat. Nos. 5,176,907;5,194,581; and 5,656,765 issued to Leong which are incorporated hereinby reference. Similar to the polyanhydrides, polyphoshate ester is beingresearched for the sole purpose of drug delivery. Unlike thepolyanhydrides, the polyphosphate esters have high molecular weights(600,000 average), yielding attractive mechanical properties. This highmolecular weight leads to transparency, and film and fiber properties.It has also been observed that the phosphorous-carbon-oxygenplasticizing effect, which lowers the glass transition temperature,makes the polymer desirable for fabrication.

The basic structure of polyphosphate ester monomer is shown below.##STR1## where P corresponds to Phosphorous, O corresponds to Oxygen,

and R and R1 are functional groups.

Reaction with water leads to the breakdown of this compound intomonomeric phosphates (phosphoric acid) and diols (see below). ##STR2##It is the hydrolytic instability of the phosphorous ester bond whichmakes this polymer attractive for controlled drug release applications.A wide range of controllable degradation rates can be obtained byadjusting the hydrophobicities of the backbones of the polymers and yetassure biodegradability.

The functional side groups allow for the chemical linkage of drugmolecules to the polymer. This is shown below. ##STR3##

The drug may also be incorporated into the backbone of the polymer.##STR4##

In summary, the highly hydrolytically reactive phosphorous ester bond,the favorable physical properties, and the versatile chemical structuremake the polyphosphate esters a superior drug delivery system for aprosthesis.

FIGS. 3A and 3B show that the filaments 12 may be made from one orseveral layers of polymer. In FIG. 3A only a single polymer is presentto carry the drugs. In FIG. 3B a second layer of polymer 15 is shown.That layer 15 may be a simple barrier which limits diffusion of drugs inthe polymer 14. In that event, the smaller molecules could elute outimmediately, while larger compounds would not elute until later when thelayer 15 has biodegraded. Alternatively, layer 15 may include adifferent drug incorporated therein from that found in layer 14. Thebarrier coating 15 could be as simple as a silicone or polyurethane.

Operation

The prosthesis is inserted into the lumen wherever needed as per theusual procedure for stents. The device is fixed into place either byradial expansion in devices such as shown in FIG. 1 or are deformed by aballoon catheter in the case of devices in accordance with FIG. 2.

FIGS. 8 through 11 show the placement and effects of the drug-elutingprosthesis of the invention. The prosthesis tacks up any intimal flapsand tears caused by any prior ballooning. The initial deposition ofplatelets and subsequent thrombus formation 38 is controlled andminimized by the stent design and the elution which limits plateletaggregation and other immediate repair responses described previously.Localized thrombus formations in the areas of cracked and roughenedplaques and newly exposed underlying collagen and fibro-muscular tissuesis also decreased. This results in limited but quick neointima formation40 and intimal proliferation over individual stent filaments progressingto mature endothelial lining. Long term significant restenosis istherefore limited. Elution of the anti-replicates along or inconjunction with the initial elution of anti-coagulants can also limitthe extent of the restenosis which occurs in the natural healingprocess.

In yet another embodiment of the invention, a purely polymericprosthesis such as that having the configuration shown in FIG. 1 can becombined with an expandable metal stent to provide additional supportfor the prosthesis. This can be important since preferred bioabsorbablepolymeric materials for the prosthesis may have insufficient resilienceto expand an occluded body lumen or to maintain its expansion. Byincluding a metal stent within the lumen of the polymeric prosthesis,the polymeric prosthesis is effectively held against the wall of thebody lumen by the strength of the metal stent. In a most preferredaspect of this embodiment, the metal stent is only temporarily implantedso that only the bioabsorbable prosthesis remains implanted in the bodylumen on a long term basis. This can be accomplished by including apolymeric stent body and a metal stent body on the distal end of acatheter designed to expand and release the stents. Both of the stentbodies have a number of support elements which make up an open-ended,radially expandable self-supporting tubular structure. In the polymericstent structure, a bioabsorbable polymeric element (such as a filmentmade from a bioabsorbable polymer) having drugs incorporated therein canbe attached to the support elements of the body so that at least aportion of the bioabsorbable element is exposed at the exterior surfaceof the polymeric stent body. The stents are arranged on the distal endof the catheter such that the catheter can provide remote, transluminaldeployment of the stents, with the metal stent inside the polymericstent, from an entry point into a selected portion of the body lumen tobe treated and also remote actuation of an expansion mechanism from theproximal end of the catheter. The expansion mechanism (e.g. a balloon orthe like if the metal stent is made of malleable metal for balloonexpansion or a release mechanism if the metal stent is a self-expandingstent made from a resilient metal) is one capable of providing radialexpansion of the metal stent body to bring the metal stent intosupporting contact with the polymeric stent body and also to press thepolymeric stent body so that it expands radially into contact with thewall of the body lumen. This will bring the bioabsorbable element intosupporting contact with a body lumen at an interior portion of the bodylumen to be treated and will position the bioabsorbable element todeliver drugs to the body lumen. Following the expansion of the stentsinto luminal contact, the balloon (if the expansion device is a balloon)can be deflated which allows luminal flow to be restored. After thestents have been in place for a predetermined period of time, the metalstent can be removed to leave only the polymeric stent (and its drugdelivery component) in position in the body lumen. This can beaccomplished, for example, by radially contracting the metal stent andthen withdrawing it from the body lumen or by unwinding the metal stenta bit at a time as it is withdrawn from the body lumen.

Referring now to specific embodiments shown in the drawings, onepossible configuration for a polymeric prosthesis supported by a metalstent is that of the prosthesis shown in FIG. 1 supported by a metalstent having a configuration such as that taught in U.S. Pat. No.4,886,062 to Wiktor which is incorporated herein by reference. Thesedevices may be combined by simply placing the polymeric prosthesis overthe metal stent and balloon; introducing the prosthesis, stent, andballoon into the body lumen as a unit until it reaches the desired pointfor expansion; inflating the balloon to radially expand the prosthesisand stent into contact with the body lumen; and removing the balloon. Insuch an embodiment, the metal stent would be permanently implanted withthe polymeric prosthesis. Another embodiment of this concept is shown inFIGS. 18 and 19a-19i in which the metal stent is only implanted for alimited period of time and then removed. Referring now to FIGS. 18 and19a-19i, a catheter assembly 50 includes a hub assembly 52 at a proximalend, an inflatable balloon 54, a metal stent 56 and a polymericprosthesis 58 at a distal end and a sheath 60 extending from theproximal to the distal end. The metal stent 56 is crimped onto theballoon 54 and includes an elongated lead 62 extending to the proximalend of the catheter assembly 50 where it includes an enlarged portion 64to enable an operator to securely grip the lead 62. Distal to theballoon 54 is the polymeric prosthesis 58 which is constrained fromradial self-expansion by the sheath 60. In operation, a guidewire 66 isinserted into the body lumen 68 and through the point of occlusion 70.The catheter assembly 50 is then passed into the lumen 68 on theguidewire 66 until the prosthesis 58 is positioned at the point of theocclusion 70. The sheath 60 is then drawn back, thereby allowing theprosthesis 58 to be pushed out of the sheath 60 by the leading edge ofthe balloon assembly where it radially self-expands into luminalcontact. The balloon 54 and stent 56 are then advanced out of the sheath60 as a unit and into the open center of the prosthesis 58. The balloon54 is then inflated to expand the metal stent 56, the prosthesis 58 andthe occlusion 70. The balloon 54 is then deflated and withdrawn from themetal stent 56 and prosthesis 58, leaving the metal stent 56 inside theprosthesis 58 in support of the prosthesis 58 and the occlusion 70. Ifthe body lumen 68 is a blood vessel, blood flow is restored by deflatingthe balloon 54. If desired, the balloon 54 can then be withdrawnentirely from the sheath 60 and also, if desired, the sheath 60 andguidewire 66 can be withdrawn. However, it is preferred to leave theballoon 54, sheath 60 and guidewire 66 in place in order to providesupport for the lead 62 and to avoid entangling the lead 62 with thecatheter lumen or guidewire 66 as they are withdrawn. If the balloon 54or guidewire 66 are to be withdrawn, it may be preferable to modify thesheath 60 by providing a separate lumen in the sheath 60 or anotherlocation in the catheter assembly 50 for the lead 62. After a desiredperiod of time which allows the prosthesis to achieve a stable supportfor the lumen, the lead 62 is pulled at the proximal end of the catheterassembly 50, thereby causing the metal stent 56 to unwind and be takenup into the sheath 60. The metal stent chosen for use in this methodshould include no edges or ends which can snag the prosthesis 58 andpull it from its intended position in the body lumen 68. The sheath isthen withdrawn, leaving the prosthesis 58 in place in the lumen 68.

This completes the description of the preferred and alternateembodiments of the invention. Those skilled in the art may recognizeother equivalents to the specific embodiments described herein whichequivalents are intended to be encompassed by the claims attachedhereto.

We claim:
 1. A device for local intralumenal administration of drugscomprising:(a) a body including a plurality of support elements forminga open-ended, radially expandable, self-supporting tubular structurehaving an interior surface and an exterior surface, the tubularstructure including as support elements a plurality of helical elements,each of which is wound in a helix configuration along a center line ofthe tubular body as a common axis, said helical elements wound inopposing helical directions such that the tubular body is variable inradial diameter under axial movement of opposite ends of the bodyrelative to each other; (b) a flexible, polymeric filament attached tothe support elements of the body, at least a portion of the filamentexposed at an exterior surface of the tubular body; (c) a drugcompounded into the polymeric filament such that the drug is deliveredto the body lumen when the tubular body is radially expanded intocontact with the portion of the body lumen to be treated; and (d) aradially expandable stent of malleable metal in supporting contact withthe tubular structure.
 2. A device for local intralumenal administrationof drugs comprising:(a) a body including a plurality of support elementsforming a open-ended, radially expandable, self-supporting tubularstructure having an interior surface and an exterior surface, thetubular structure including as support elements a plurality of helicalelements, each of which is wound in a helix configuration along a centerline of the tubular body as a common axis, said helical elements woundin opposing helical directions such that the tubular body is variable inradial diameter under axial movement of opposite ends of the bodyrelative to each other; (b) a flexible, polymeric filament attached tothe support elements of the body, at least a portion of the filamentexposed at an exterior surface of the tubular body; (c) a drugcompounded into the polymeric filament such that the drug is deliveredto the body lumen when the tubular body is radially expanded intocontact with the portion of the body lumen to be treated; and (d) aradially expandable stent of resilient metal in supporting contact withthe tubular structure.
 3. A device for local intralumenal administrationof drugs comprising:(a) a body including a plurality of bioabsorbablepolymeric elements forming an open-ended, radially expandable tubularstructure having an interior surface and an exterior surface, thetubular structure including a plurality of elements joined together suchthat the tubular body is variable in radial diameter; (b) a flexible,bioabsorbable polymeric filament attached to the elements of the bodysuch that at least a portion of the filament is exposed at an exteriorsurface of the tubular body; (c) a drug compounded into the polymericfilament such that the drug is delivered to the body lumen when thetubular body is radially expanded into contact with the portion of thebody lumen to be treated; and (d) a radially expandable metal stent insupporting contact with the tubular body.
 4. The device of claim 3 alsocomprising a barrier coating of polymeric material on thedrug-containing filament to limit the rate of drug elution.
 5. Thedevice of claim 3 wherein the drug is selected from the group consistingof antiplatelet drugs, anticoagulant drugs, anti-inflammatory drugs,antireplicate drugs and combinations of said drugs.
 6. The device ofclaim 3 wherein the stent is a radially expandable stent of malleablemetal.
 7. The device of claim 3 wherein the stent is a radiallyexpandable stent of resilient metal.
 8. The device of claim 3 whereinthe elements of the tubular body are joined together by weaving andwherein the flexible, polymeric filament is woven into the supportelements of the tubular body.
 9. The device of claim 3 wherein thepolymeric filament is attached to the elements of the tubular body by abonded juncture.